Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms.

Molecular Cell
Nicholas C HustonAnna Marie Pyle

Abstract

Severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) is the positive-sense RNA virus that causes coronavirus disease 2019 (COVID-19). The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form RNA structures, yet as much as 97% of its 30 kilobases have not been structurally explored. Here, we apply a novel long amplicon strategy to determine the secondary structure of the SARS-CoV-2 RNA genome at single-nucleotide resolution in infected cells. Our in-depth structural analysis reveals networks of well-folded RNA structures throughout Orf1ab and reveals aspects of SARS-CoV-2 genome architecture that distinguish it from other RNA viruses. Evolutionary analysis shows that several features of the SARS-CoV-2 genomic structure are conserved across β-coronaviruses, and we pinpoint regions of well-folded RNA structure that merit downstream functional analysis. The native, secondary structure of SARS-CoV-2 presented here is a roadmap that will facilitate focused studies on the viral life cycle, facilitate primer design, and guide the identification of RNA drug targets against COVID-19.

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Citations

Dec 4, 2020·Journal of Virology·Rafael de Cesaris Araujo TavaresAnna Marie Pyle
May 8, 2021·Accounts of Chemical Research·Kevin M Weeks
May 28, 2021·Journal of the American Chemical Society·Sandro BottaroKresten Lindorff-Larsen
May 9, 2021·Journal of Virology·Valeria LullaBen F Luisi
May 29, 2021·NAR Genomics and Bioinformatics·Ryan J AndrewsWalter N Moss
May 22, 2021·Evolutionary Bioinformatics Online·Sean P RyderFrancesca Massi
Jun 26, 2021·Nature Communications·Changchang CaoYuanchao Xue
Jun 30, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yu SunJunjie U Guo
Jul 21, 2021·Journal of the American Chemical Society·Tamar SchlickAlain Laederach
Aug 11, 2021·Scientific Reports·Clément Gilbert, Torstein Tengs
Aug 18, 2021·Nucleic Acids Research·Meredith N FrazierRobin E Stanley
Aug 28, 2021·NAR Genomics and Bioinformatics·Pierce RadeckiSharon Aviran

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Datasets Mentioned

BETA
GSE154171
MN908947
MN908947.3
MG772934.1
JX993987.1
DQ022305.2
DQ648857.1
AY515512.1
AY274119.3
GU553363.1

Methods Mentioned

BETA
SHAPE-MaP
PCR
Assay
transfection

Software Mentioned

RAFSp
Jalview
Superfold
R
SHAPEKnots
ShapeMapper
Rscape
IGV
RNA structure
Scape

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